Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men

The pharmacokinetics, efficacy, and safety of the Androderm testosterone (T ) transdermal system (TTD) and intramuscular T enanthate injections (IM) fo r the treatment of male hypogonadism were compared in a 24-week multicenter , randomized, parallel-group study. Sixty-six adult hypogonadal men (22-65 years of age) were withdrawn from prior IM treatment for 4-6 weeks and then randomly assigned to treatment with TTD (two 2.5-mg systems applied nightl y) or IM (200 mg injected every 2 weeks); there were 33 patients per group. Twenty-six patients in the TTD group and 32 in the IM group completed the study. TTD treatment produced circadian variations in the levels of total T, bioav ailable T, dihydrotestosterone, and estradiol within the normal physiologic al ranges. IM treatment produced supraphysiological levels of T, bioavailab le T, and estradiol (but not dihydrotestosterone) for set-cat days after ea ch injection. Mean morning sex hormone levels were within the normal range in greater proportions of TTD patients (range, 77-100%) than IM patients (r ange, 19-84%). Both treatments normalized LH levels in approximately 50% of patients with primary hypogonadism; however, LH levels were suppressed to the subnormal range in 31% of IM patients us. 0% of TTD patients. Both trea tments maintained sexual function (assessed by questionnaire and Rigiscan) and mood (Beck Depression Inventory) at the prior treatment levels. Prostate-specific antigen levels, prostate volumes, and lipid and serum che mistry parameters were comparable in both treatment groups. Transient shin irritation from the patches was reported by 60% of the TTD patients, but ca used only three patients (9%) to discontinue treatment. Ih I treatment prod uced local reactions in 33% of patients and was associated with significant ly more abnormal hematocrit elevations (43.8% of patients) compared with TT D treatment (15.4% of patients). Gynecomastia resolved more frequently duri ng TTD treatment (4 of 10 patients) than with IM treatment (1 of 9 patients ). Although both treatments seem to be efficacious for replacing T in hypogona dal men, the more physiological sex hormone levels and profiles associated with TTD may offer possible advantages over IM in minimizing excessive stim ulation of erythropoiesis, preventing/ ameliorating gynecomastia, and not o ver-suppressing gonadotropins.